A型流感病毒(influenza A virus,IAV)完全依赖于宿主蛋白完成自身的生命周期。然而,调控其膜蛋白转运的分子机制尚不清楚。2025年7月8日,华中农业大学周红波教授带领的研究团队在Nature Communications上发表了题为“Rab27a regulates t...A型流感病毒(influenza A virus,IAV)完全依赖于宿主蛋白完成自身的生命周期。然而,调控其膜蛋白转运的分子机制尚不清楚。2025年7月8日,华中农业大学周红波教授带领的研究团队在Nature Communications上发表了题为“Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane”的研究论文,揭示了Rab27a及其效应分子SYTL1和SYTL4通过促进流感病毒膜蛋白转运从而有利于病毒粒子出芽的分子机制。展开更多
OBJECTIVE:To explore the effect of Chang’an decoction(肠安方,CAD)of ameliorating the immune imbalances in ulcerative colitis(UC)by regulating Rab27 in the P53/high mobility group box 1 pathway.METHODS:The functions a...OBJECTIVE:To explore the effect of Chang’an decoction(肠安方,CAD)of ameliorating the immune imbalances in ulcerative colitis(UC)by regulating Rab27 in the P53/high mobility group box 1 pathway.METHODS:The functions and important signaling pathways of the Rab27-and UC-related genes were analyzed viathe use of microarray data from the gene expression omnibus database,gene ontology database,Kyoto encyclopedia of genes and genomes database and gene set enrichment analysis.Dextran sulfate sodium salt-induced colitis mouse model was used to verify the bioinformatics results.Colon length,body weight,and disease activity index were measured.Hematoxylin and eosin staining was applied to validate the histopathology.Tight junction proteins were detected by immunohistochemistry.The proportions of T helper 17 cells(Th17)and regulatory T cells(Treg)in mesenteric lymph nodes were measured viaflow cytometry.Proinflammatory cytokines like interleukin(IL)17(IL-17),IL-21 and IL-22 and anti-inflammatory cytokines like transforming growth factorβand IL-10 in the serum and colon of mice were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction,respectively.The expression levels of high mobility group box 1(HMGB1),P53 and phospho-P53(P-P53)in colonic tissues were detected by immunofluorescence and Western blotting.RESULTS:Bioinformatics analysis revealed that compared with normal tissues,the expression of Rab27 was significantly increased in UC tissues.Receiver operating characteristic curve showed that Rab27 has the potential to be used as a biomarker for the diagnosis of disease activity.Enrichment analysis showed that UC and Rab27 were mainly associated with small molecule transport,nutrient metabolism,transmembrane transport and the downstream pathway of P53.According to animal experiments,the expression of Rab27 was increased in UC tissues,which aggravated the colonic pathological damage,activated the expression of HMGB1,and also leaded to the imbalance of Th17 and Treg cells.After CAD intervention,Rab27 overexpression,weight loss,colon shortening,and pathological damage were substantial reduced,the expression of tight junction proteins,zona occludens 1 and Occludin were increased.The effect of CAD at high-dose was more obvious.In addition,CAD upgraded the number of Treg cells and the production of TGF-βand IL-10,while decreasing the number of Th17 cells and the expression of inflammatory cytokines(IL-17,IL-21,and IL-22).Moreover,colon inflammation was alleviated by CAD,as indicated by the regulation of HMGB1 and P-P53 expression.CONCLUSION:The expression of Rab27,HMGB1 and P-P53 could be decreased by CAD,and the balance of Th17 and Treg cells as well as their related cytokines could be regulated by CAD.展开更多
AIM:To investigate the association of Rab27A and Rab27B expression with clinicopathological characteristics and prognosis of hepatocellular carcinoma(HCC).METHODS:We used reverse transcription polymerase chain reactio...AIM:To investigate the association of Rab27A and Rab27B expression with clinicopathological characteristics and prognosis of hepatocellular carcinoma(HCC).METHODS:We used reverse transcription polymerase chain reaction(RT-PCR),real-time PCR,and Western blotting to detect Rab27A and Rab27B mRNA and protein expression in 5 human HCC lines and the immortalized hepatic HL-7702 cell line.We further examined 148 primary HCC samples matched with adjacent normal tissue and 80 non-HCC specimens by immunohistochemistry to evaluate the correlation of Rab27A and Rab27B expression with clinicopathological features and prognosis.RESULTS:Our data showed that Rab27A and Rab27Bwere differentially expressed in cell lines and primary HCC tumors.Rab27A mRNA and protein were detected in 67%(4/6)of human cell lines and 80%(4/5)of HCC cell lines,while Rab27B was found in 50%(3/6)of human lines and 40%(2/5)of HCC lines.Rab27A expression was higher in primary HCC(46.2%,66/143)than in matched adjacent tissue(24.3%,33/136,P<0.001),whereas immunopositivity for Rab27B was lower in primary HCC(57.4%,81/141)than in matched adjacent tissue(87.5%,119/136,P<0.001).Analysis of clinicopathological characteristics of 148 HCC specimens revealed significant correlations between Rab27A and Rab27B expression and tumor tumor-node-metastasis(TNM)classification(P=0.046 and P=0.027,respectively),and between strong Rab27A expression and tumor differentiation grade(P=0.008).Survival analyses revealed that patients with Rab27A+or Rab27B+tumors had significantly reduced overall survival compared with that of patients with Rab27A-or Rab27B-tumors(P= 0.015 and P=0.005,respectively).Risk analyses revealed that Rab27B+and TNMⅢ-Ⅳwere independent poor prognosis factors associated with a 3.36-and 3.37fold higher relative risk of death,respectively.CONCLUSION:Rab27A and Rab27B expression were closely correlated with tumor progression and can be valuable prognostic indicators for HCC patients.展开更多
Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were e...Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion （DRG） neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/ Slp2-a complex affects Schwann cell myelination in vitro.展开更多
文摘A型流感病毒(influenza A virus,IAV)完全依赖于宿主蛋白完成自身的生命周期。然而,调控其膜蛋白转运的分子机制尚不清楚。2025年7月8日,华中农业大学周红波教授带领的研究团队在Nature Communications上发表了题为“Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane”的研究论文,揭示了Rab27a及其效应分子SYTL1和SYTL4通过促进流感病毒膜蛋白转运从而有利于病毒粒子出芽的分子机制。
基金Supported by Lingnan Medical Research Center of Guangzhou University of Chinese MedicineNational Natural Science Foundation of China:Mechanism of Chang’an Decoction in Intestinal Mucosal Immunity of Ulcerative Colitis on Exocrine Mediated Rab27(81903963)Natural Science Foundation of Guangdong Province:the Role of the Neuropeptide Spexin-associated Gycogen Synthase Kinase-3βSignaling Pathway in Regulating the Enteric Nervous-immune Network in Ulcerative Colitis and the Intervention Mechanism of Chang’an Formula(2018A030310614)。
文摘OBJECTIVE:To explore the effect of Chang’an decoction(肠安方,CAD)of ameliorating the immune imbalances in ulcerative colitis(UC)by regulating Rab27 in the P53/high mobility group box 1 pathway.METHODS:The functions and important signaling pathways of the Rab27-and UC-related genes were analyzed viathe use of microarray data from the gene expression omnibus database,gene ontology database,Kyoto encyclopedia of genes and genomes database and gene set enrichment analysis.Dextran sulfate sodium salt-induced colitis mouse model was used to verify the bioinformatics results.Colon length,body weight,and disease activity index were measured.Hematoxylin and eosin staining was applied to validate the histopathology.Tight junction proteins were detected by immunohistochemistry.The proportions of T helper 17 cells(Th17)and regulatory T cells(Treg)in mesenteric lymph nodes were measured viaflow cytometry.Proinflammatory cytokines like interleukin(IL)17(IL-17),IL-21 and IL-22 and anti-inflammatory cytokines like transforming growth factorβand IL-10 in the serum and colon of mice were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction,respectively.The expression levels of high mobility group box 1(HMGB1),P53 and phospho-P53(P-P53)in colonic tissues were detected by immunofluorescence and Western blotting.RESULTS:Bioinformatics analysis revealed that compared with normal tissues,the expression of Rab27 was significantly increased in UC tissues.Receiver operating characteristic curve showed that Rab27 has the potential to be used as a biomarker for the diagnosis of disease activity.Enrichment analysis showed that UC and Rab27 were mainly associated with small molecule transport,nutrient metabolism,transmembrane transport and the downstream pathway of P53.According to animal experiments,the expression of Rab27 was increased in UC tissues,which aggravated the colonic pathological damage,activated the expression of HMGB1,and also leaded to the imbalance of Th17 and Treg cells.After CAD intervention,Rab27 overexpression,weight loss,colon shortening,and pathological damage were substantial reduced,the expression of tight junction proteins,zona occludens 1 and Occludin were increased.The effect of CAD at high-dose was more obvious.In addition,CAD upgraded the number of Treg cells and the production of TGF-βand IL-10,while decreasing the number of Th17 cells and the expression of inflammatory cytokines(IL-17,IL-21,and IL-22).Moreover,colon inflammation was alleviated by CAD,as indicated by the regulation of HMGB1 and P-P53 expression.CONCLUSION:The expression of Rab27,HMGB1 and P-P53 could be decreased by CAD,and the balance of Th17 and Treg cells as well as their related cytokines could be regulated by CAD.
文摘AIM:To investigate the association of Rab27A and Rab27B expression with clinicopathological characteristics and prognosis of hepatocellular carcinoma(HCC).METHODS:We used reverse transcription polymerase chain reaction(RT-PCR),real-time PCR,and Western blotting to detect Rab27A and Rab27B mRNA and protein expression in 5 human HCC lines and the immortalized hepatic HL-7702 cell line.We further examined 148 primary HCC samples matched with adjacent normal tissue and 80 non-HCC specimens by immunohistochemistry to evaluate the correlation of Rab27A and Rab27B expression with clinicopathological features and prognosis.RESULTS:Our data showed that Rab27A and Rab27Bwere differentially expressed in cell lines and primary HCC tumors.Rab27A mRNA and protein were detected in 67%(4/6)of human cell lines and 80%(4/5)of HCC cell lines,while Rab27B was found in 50%(3/6)of human lines and 40%(2/5)of HCC lines.Rab27A expression was higher in primary HCC(46.2%,66/143)than in matched adjacent tissue(24.3%,33/136,P<0.001),whereas immunopositivity for Rab27B was lower in primary HCC(57.4%,81/141)than in matched adjacent tissue(87.5%,119/136,P<0.001).Analysis of clinicopathological characteristics of 148 HCC specimens revealed significant correlations between Rab27A and Rab27B expression and tumor tumor-node-metastasis(TNM)classification(P=0.046 and P=0.027,respectively),and between strong Rab27A expression and tumor differentiation grade(P=0.008).Survival analyses revealed that patients with Rab27A+or Rab27B+tumors had significantly reduced overall survival compared with that of patients with Rab27A-or Rab27B-tumors(P= 0.015 and P=0.005,respectively).Risk analyses revealed that Rab27B+and TNMⅢ-Ⅳwere independent poor prognosis factors associated with a 3.36-and 3.37fold higher relative risk of death,respectively.CONCLUSION:Rab27A and Rab27B expression were closely correlated with tumor progression and can be valuable prognostic indicators for HCC patients.
基金supported by the National Natural Science Foundation of China,No.31071251,81471255,and 81471259a grant from the Ministry of Science and Technology of China(973 Program),No.2014CB542202+2 种基金a grant from the Basic Research Program of Education Department of Jiangsu Province,China,No.14KJA310004a grant from the Natural Science Research Project of Nantong Science and Technology Bureau,China,No.HS2013014a grant from the Natural Science Research Project of Nantong University,China,No.13Z008
文摘Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion （DRG） neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/ Slp2-a complex affects Schwann cell myelination in vitro.
